Phelan-McDermid syndrome is a genetic developmental disorder. It results in neuromuscular symptoms and severe intellectual disability.
What is Phelan-McDermid syndrome?
In the medical community, Phelan-McDermid syndrome (PMS) is also known as microdeletion 22q13.3 or 22q13.3 deletion syndrome. This refers to a genetically caused developmental disorder associated with intellectual disability, neuromuscular complaints, and a lack of language development. Responsible for the disorder is a microdeletion on chromosome 22, on the long arm of which a segment is missing. Phelan-McDermid syndrome is one of the very rare diseases. The developmental disorder has only been diagnosed about one thousand times in the world. However, medical experts assume that the number is too low, because the majority of all patients suffer from autism spectrum disorders. However, not all PMS cases are associated with autism, so epidemiological estimates tend to be inaccurate. The syndrome emerges as early as childhood. Phelan-McDermid syndrome was named after the researchers K. Phelan and H. McDermid, through whom the syndrome was characterized in a more phenotypically accurate way. The first description of the developmental disorder occurred in 1985 as partial monosomy 22q.
Causes
Phelan-McDermid syndrome is responsible for the loss of genetic material from chromosome 22. Thus, affected individuals lack a segment at the end of the long chromosomal arm. Three causes can be considered for this genetic disorder. These include simple deletion, in which part of chromosome 22 breaks off during the formation of a sperm cell or an egg cell. Ring chromosome formation is also possible, in which there is breakage of both ends of chromosome 22. Subsequently, a connection between the open ends occurs to form a chromosome that has the shape of a ring. The third possible cause is unbalanced translocations. In this case, there is a loss of part of chromosome 22, and the segment of another chromosome steps in as a replacement. The missing segment of chromosome 22 contains the gene PROSAP2/SHANK 3. It is suspected that the absence of this gene is responsible for the neurological symptoms of Phelan-McDermid syndrome. Observations made in recent years suggest that this is the case. A copy of the Shank3 gene is missing in almost all of the cases described.
Symptoms, complaints, and signs
The symptoms caused by Phelan-McDermid syndrome are varied and turn out differently from person to person. However, almost all patients have a global developmental disorder. This results in severe mental retardation and marked muscle hypotonia. Furthermore, language development suffers from the syndrome. The psychiatric component is considered inconsistent. Early childhood autism or autism spectrum disorders can be identified in about 80 percent of all affected children. In some affected individuals, who have a mutation in the Shank3 gene or a microdeletion 22q13.3, schizophrenia or bipolar disorder sets in during adolescence or adulthood. The speech disorder becomes apparent very early in those affected. Thus, the sounds are made only with a delay or are completely absent. In some cases, the children are quite capable of initially uttering a few words or even individual sentences. With increasing age, however, they lose this ability more and more. Other typical features of Phelan-McDermid syndrome are a tendency to infections and an increased pain tolerance. The first symptom of the syndrome in babies is muscular hypotonia. It is not uncommon to see slight malformations of the face and limbs. Furthermore, malformations in the interior of the body such as in the [[kidneys, the urinary tract or the heart are possible. For this reason, appropriate control examinations should take place. Epileptic seizures occur in about 25 percent of all children suffering from Phelan-McDermid syndrome. These may be associated with malformations of the brain such as arachnoid cysts. Rarely, disorders of internal or endocrine organs, such as autoimmune hepatitis, become apparent. The mental disabilities that result from Phelan-McDermid syndrome also affect the behavior of affected children. For example, they lack social reciprocity and eye contact.Many children also lack a biphasic sleep-wake rhythm.
Diagnosis and course of the disease
To diagnose Phelan-McDermid syndrome, a blood test is usually performed. This involves a special test called a CGH array. CGH stands for Comparative Genomic Hybridization. With the help of this CGH test, it is possible to detect chromosomal changes, even if they are so small that they cannot be detected in a normal chromosome analysis. Furthermore, PMS can also be detected by pregnancy tests such as amniocentesis. The prognosis for Phelan-McDermid syndrome is negative because the developmental disorder cannot be cured. However, the patient’s life expectancy does not usually suffer. Thus, it depends on the care the patient receives and the extent of his or her disabilities.
Complications
Due to Phelan-McDermid syndrome, affected individuals suffer from significantly delayed development and also various disorders in growth. Usually, this also results in significant mental and motor disabilities and limitations. In many cases of Phelan-McDermid syndrome, the patient’s relatives and parents also suffer from the psychological symptoms and also from depression, so that the quality of life of the entire family is significantly reduced. Likewise, Phelan-McDermid syndrome results in muscle atrophy and also mental limitations, so that the children are schizophrenic or suffer from bipolar disorder. The ability to speak is also significantly limited by the syndrome, so that there are difficulties in communication. Furthermore, in many cases, malformations of the kidneys or heart also occur with this syndrome, which may possibly reduce the life expectancy of the patient. This leads to epileptic seizures and various skin complaints . Unfortunately, Phelan-McDermid syndrome cannot be treated causally. For this reason, treatment is mainly based on the symptoms of this syndrome. There are no particular complications, but not all symptoms can be limited. Possibly, Phelan-McDermid syndrome will also reduce the life expectancy of the affected person.
When should you see a doctor?
Because Phelan-McDermid syndrome is a serious genetic disorder, it must always be examined and treated by a doctor. Only medical treatment can limit the symptoms. However, a complete cure is not possible, so that the affected person suffers from the symptoms of this syndrome for the rest of his life. A doctor should be consulted for Phelan-McDermid syndrome if the patient suffers from muscle discomfort and especially severe muscle pain. The condition can lead to mental retardation or bipolar disorder. If these symptoms also occur, the patient should undergo medical treatment to avoid further complications. Early treatment can significantly limit mental retardation. Furthermore, regular examinations of the organs are useful, since the heart and kidneys are also affected by the disease. In the event of an epileptic seizure, an emergency doctor should be notified immediately or a hospital should be visited. Since parents and relatives also often suffer from psychological discomfort due to Phelan-McDermid syndrome, psychological care is very useful.
Treatment and therapy
Treatment of the causes of Phelan-McDermid syndrome is not possible. Therefore, symptomatic therapy takes place. Promoting cognitive, motor, language, and social factors plays an important role in improving the quality of life of those affected. It is also important to treat accompanying symptoms such as swallowing and sucking disorders, reflux or vomiting, which already occur in early childhood due to muscular hypotonia. Further measures for early intervention include physiotherapeutic treatment, the use of speech output
Speech output computers, or occupational therapy may be considered.
Outlook and prognosis
The prognosis for Phelan-McDermid syndrome is poor on one hand and good on the other. It is true that the disease is not curable. However, it often does not limit the life expectancy of those affected.However, if the degree of disability caused by Phelan-McDermid syndrome is higher and medical and psychosocial care remains inadequate, the prognosis can be significantly worse. The sooner the affected children are supported in their intellectual or motor development, the better the prognosis. Apart from this, however, only symptomatic treatment can be given to the affected individuals. In the course of Phelan-McDermid syndrome, neurological or psychiatric abnormalities such as depression, schizophrenia or bipolar disorder may develop. These sequelae can be treated according to established medical standards. However, concomitant drug treatments do not work as well in these patients as in others. The prognosis is worsened by lack of support, insufficient medical care, lack of recognition in the social sphere, and concomitant epilepsies or skin symptoms. In addition, medical complications may occur. For example, Phelan-McDermid syndrome can lead to malformations of important organs or muscle atrophy. Such malformations often affect the heart or kidneys. Such sequelae can negatively affect the quality of life and life span of those affected. In this case, the medical prognosis may be better than the self-assessment of the affected person.
Prevention
Phelan-McDermid syndrome is already congenital. Therefore, no preventive measures are possible.
Follow-up care
In most cases, affected individuals with Phelan-McDermid syndrome have either no follow-up care at all or only very limited follow-up care measures available. Affected individuals should seek medical attention early in the course of this disease, as it may not heal on its own. Early diagnosis of the disease can therefore prevent further complications and discomfort. In case of a desire to have children, a genetic examination and counseling should always be done first, so that the syndrome cannot reoccur in the descendants, as it is a genetic disease. The affected person should consult a doctor at the first signs and symptoms of the disease. Most patients are dependent on the measures of physiotherapy or physiotherapy for Phelan-McDermid syndrome. Many of the exercises from such therapies can also be performed in the patient’s own home, possibly speeding healing. Likewise, affected children depend on intensive care and support from their own family to alleviate symptoms and allow the child to develop. As a rule, no general statement can be made about the further course and prediction of the life expectancy of the disease in this context.
What you can do yourself
The therapy of Phelan-Mc-Dermid syndrome is primarily aimed at early support of the child with the disease. The most important measure is to specifically promote the patient’s social, motor, linguistic, and cognitive abilities. This requires sports, physiotherapy, mental training and a number of other measures. Parents should contact the relevant doctors at an early stage so that a treatment plan can be drawn up that takes into account the complex symptoms of Phelan-Mc-Dermid syndrome. In addition, adjustments must be made in everyday life. The children with the disease are usually unable to move around without help and accordingly require outpatient care. Stairs suitable for the disabled must be installed in the household and other changes made depending on the symptom picture. In addition, the child usually needs a wheelchair. In this case, insurance-related questions must be clarified, whereby the responsible physician is also available to provide support in this aspect. The parents of the affected children are usually exposed to a lot of stress. This makes accompanying discussions with other affected persons and, if necessary, with a therapist all the more important. General measures such as sports, relaxation exercises and a balanced diet help to reduce stress.